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Synovial expression of IL-15 in rheumatoid arthritis is not influenced by blockade of tumour necrosis factor.
Arthritis Res Ther. 2006; 8(1):R18.AR

Abstract

Blockade of tumour necrosis factor (TNF) is an effective treatment in rheumatoid arthritis (RA), but both non-responders and partial responders are quite frequent. This suggests that other pro-inflammatory cytokines may be of importance in the pathogenesis of RA and as possible targets for therapy. In this study we investigated the effect of TNF blockade (infliximab) on the synovial expression of IL-15 in RA in relation to different cell types and expression of other cytokines, to elucidate whether or not IL-15 is a possible target for therapy, independently of TNF blockade. Two arthroscopies with multiple biopsies were performed on nine patients with RA and knee-joint synovitis before and after three infusions of infliximab (3 mg/kg). Synovial biopsies were analysed with immunohistochemistry for expression of IL-15, TNF, IL-1alpha, IL-1ss and IFN-gamma, and for the cell surface markers CD3, CD68 and CD163. Stained synovial biopsy sections were evaluated by computerized image analysis. IL-15 expression was detected in all synovial biopsies taken at baseline. After infliximab therapy, the expression of IL-15 was increased in four patients and reduced in five. Synovial expression of IL-15 was not correlated with any CD marker or with the presence of any other cytokine. Synovial cellularity was decreased after 8 to 10 weeks of treatment with a significant reduction of the CD68-positive synovial cells, whereas no significant change was seen in the number of CD3-positive T cells and CD163-expressing macrophages. The number of TNF-producing cells in the synovial tissue at baseline was correlated with a good response to therapy. Thus, in this study the synovial expression of IL-15 in RA was not consistently influenced by TNF blockade, being apparently independent of TNF expression in the synovium. Consequently, we propose that IL-15 should remain as a therapeutic target in RA, regardless of the response to TNF blockade.

Authors+Show Affiliations

Department of Rheumatology, Karolinska University Hospital, S-141 86 Stockholm, Sweden. sofia.ernestam@karolinska.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16507118

Citation

Ernestam, Sofia, et al. "Synovial Expression of IL-15 in Rheumatoid Arthritis Is Not Influenced By Blockade of Tumour Necrosis Factor." Arthritis Research & Therapy, vol. 8, no. 1, 2006, pp. R18.
Ernestam S, af Klint E, Catrina AI, et al. Synovial expression of IL-15 in rheumatoid arthritis is not influenced by blockade of tumour necrosis factor. Arthritis Res Ther. 2006;8(1):R18.
Ernestam, S., af Klint, E., Catrina, A. I., Sundberg, E., Engström, M., Klareskog, L., & Ulfgren, A. K. (2006). Synovial expression of IL-15 in rheumatoid arthritis is not influenced by blockade of tumour necrosis factor. Arthritis Research & Therapy, 8(1), R18.
Ernestam S, et al. Synovial Expression of IL-15 in Rheumatoid Arthritis Is Not Influenced By Blockade of Tumour Necrosis Factor. Arthritis Res Ther. 2006;8(1):R18. PubMed PMID: 16507118.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synovial expression of IL-15 in rheumatoid arthritis is not influenced by blockade of tumour necrosis factor. AU - Ernestam,Sofia, AU - af Klint,Erik, AU - Catrina,Anca Irinel, AU - Sundberg,Erik, AU - Engström,Marianne, AU - Klareskog,Lars, AU - Ulfgren,Ann-Kristin, PY - 2005/07/08/received PY - 2005/10/06/revised PY - 2005/11/21/accepted PY - 2006/3/2/pubmed PY - 2007/1/30/medline PY - 2006/3/2/entrez SP - R18 EP - R18 JF - Arthritis research & therapy JO - Arthritis Res Ther VL - 8 IS - 1 N2 - Blockade of tumour necrosis factor (TNF) is an effective treatment in rheumatoid arthritis (RA), but both non-responders and partial responders are quite frequent. This suggests that other pro-inflammatory cytokines may be of importance in the pathogenesis of RA and as possible targets for therapy. In this study we investigated the effect of TNF blockade (infliximab) on the synovial expression of IL-15 in RA in relation to different cell types and expression of other cytokines, to elucidate whether or not IL-15 is a possible target for therapy, independently of TNF blockade. Two arthroscopies with multiple biopsies were performed on nine patients with RA and knee-joint synovitis before and after three infusions of infliximab (3 mg/kg). Synovial biopsies were analysed with immunohistochemistry for expression of IL-15, TNF, IL-1alpha, IL-1ss and IFN-gamma, and for the cell surface markers CD3, CD68 and CD163. Stained synovial biopsy sections were evaluated by computerized image analysis. IL-15 expression was detected in all synovial biopsies taken at baseline. After infliximab therapy, the expression of IL-15 was increased in four patients and reduced in five. Synovial expression of IL-15 was not correlated with any CD marker or with the presence of any other cytokine. Synovial cellularity was decreased after 8 to 10 weeks of treatment with a significant reduction of the CD68-positive synovial cells, whereas no significant change was seen in the number of CD3-positive T cells and CD163-expressing macrophages. The number of TNF-producing cells in the synovial tissue at baseline was correlated with a good response to therapy. Thus, in this study the synovial expression of IL-15 in RA was not consistently influenced by TNF blockade, being apparently independent of TNF expression in the synovium. Consequently, we propose that IL-15 should remain as a therapeutic target in RA, regardless of the response to TNF blockade. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/16507118/Synovial_expression_of_IL_15_in_rheumatoid_arthritis_is_not_influenced_by_blockade_of_tumour_necrosis_factor_ L2 - https://arthritis-research.biomedcentral.com/articles/10.1186/ar1871 DB - PRIME DP - Unbound Medicine ER -